Cannabidiol (CBD) appears to be the reigning poster child of cannabis lately–but can it mitigate the side effects of tetrahydrocannabinol (THC)? This is an area of interest among cannabis scientists (and patients) as it can pave way for the development of safe cannabinoid-based medicines.
THC and CBD are common phytocannabinoids found in cannabis that share similar molecular structures. However, the important difference between them lies within a single chemical bond.
And guess what?
This is what makes THC psychoactive (intoxicating) and CBD non-psychoactive (or non-intoxicating) because it affects the way each compound binds to receptors in the brain.
CBD is a allosteric modulator of the cannabinoid 1 (CB1) receptor. While THC is a partial agonist at this receptor, CBD modifies the shape of this receptor, thereby limiting THC’s ability to bind.
While many enjoy THC’s effects, some people experience unwanted results such as short-term memory loss and anxiety. Additionally, patients who use cannabis may not want to get intoxicated while medicating.
So, is there any way to mitigate these effects, perhaps by taking CBD with THC? Studies (and anecdotes) point to yes.
A recent study conducted by the University of Western Ontario identified the mechanism through which CBD blocks side effects caused by THC.
Steven Laviolette, PhD and his team of researchers used pre-clinical models to study a molecule in the brain’s hippocampus (or memory center) called extracellular-signal regulated kinase (ERK). This molecule has been associated with the neuropsychiatric effects of THC.
The results of this study which were published in the Journal of Neuroscience showed the following:
- THC administration increased levels of activated ERK, resulting in anxious behavior
- CBD and THC administration normalized ERK levels, leading to less anxious behavior
The researchers concluded that CBD modulates the effects of THC on the ERK pathway; in this way, it mitigates THC’s effects.
The results from this study and others warrant further investigation to inform pharmaceutical application. For example, Sativex (a cannabis-based drug), which is approved to treat spasticity associated with multiple sclerosis in the UK, contains both CBD and THC in a ratio of 1:1. The addition of CBD to THC potentiates the therapeutic benefits of THC while attenuating some of its unwanted effects.
CBD and THC hold enormous potential for treating a multitude of conditions but we’re still teasing out their separate and combined effects on both the body and brain.
1. Laprairie B. Cannabidiol is a negative allosteric modulator of the cannabinoid CB1 receptor. Br J Pharmacol. 2015;172(20):4790-4805.
2. Laviolette S., et al. Cannabidiol counteracts the psychotropic side-effects of Δ-9-tetrahydrocannabinol in the ventral hippocampus through bidirectional control of ERK1-2 phosphorylation. Journal of Neuroscience. 2019;39(44):8762-8777.